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PMID: 21478889 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural

A framework for variation discovery and genotyping using next-generation DNA sequencing data.

Nature genetics ·Vol. 43 ·No. 5 ·2011-05-00 ·Pages 491-8

DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, del Angel G, Rivas MA, Hanna M, McKenna A, Fennell TJ, Kernytsky AM, Sivachenko AY, Cibulskis K, Gabriel SB, Altshuler D, Daly MJ

Abstract

Recent advances in sequencing technology make it possible to comprehensively catalog genetic variation in population samples, creating a foundation for understanding human disease, ancestry and evolution. The amounts of raw data produced are prodigious, and many computational steps are required to translate this output into high-quality variant calls. We present a unified analytic framework to discover and genotype variation among multiple samples simultaneously that achieves sensitive and specific results across five sequencing technologies and three distinct, canonical experimental designs. Our process includes (i) initial read mapping; (ii) local realignment around indels; (iii) base quality score recalibration; (iv) SNP discovery and genotyping to find all potential variants; and (v) machine learning to separate true segregating variation from machine artifacts common to next-generation sequencing technologies. We here discuss the application of these tools, instantiated in the Genome Analysis Toolkit, to deep whole-genome, whole-exome capture and multi-sample low-pass (∼4×) 1000 Genomes Project datasets.

MeSH Terms
Data Interpretation, Statistical Databases, Nucleic Acid Exons Genetic Variation Genetics, Population/methods,statistics & numerical data Genome, Human Genotype Humans Polymorphism, Single Nucleotide Sequence Alignment/methods,statistics & numerical data Sequence Analysis, DNA/methods,statistics & numerical data Software
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
DePristo Mark A
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. depristo@broadinstitute.org
Banks Eric
Poplin Ryan
Garimella Kiran V
Maguire Jared R
Hartl Christopher
Philippakis Anthony A
del Angel Guillermo
Rivas Manuel A
Hanna Matt
McKenna Aaron
Fennell Tim J
Kernytsky Andrew M
Sivachenko Andrey Y
Cibulskis Kristian
Gabriel Stacey B
Altshuler David
Daly Mark J
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.806
Email
depristo@broadinstitute.org
Published
2011-05-00
Epub
2011-00-10
Pages
491-8
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3083463
Subset
IM
Grants
NHGRI NIH HHS · U54 HG003067-01 · United States
NHGRI NIH HHS · U01 HG005208-01 · United States
NIDDK NIH HHS · P30 DK043351 · United States
NHGRI NIH HHS · 54 HG003067 · United States
NHGRI NIH HHS · U54 HG003067 · United States
NHGRI NIH HHS · U01 HG005208 · United States
External Links
PubMed source DOI: 10.1038/ng.806 PMC Full Text View journal details
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